H. pylon, an infection approaching 100 percent in developing countries, has been strongly linked epidemiologically to gastric cancer, but the mechanism and cofactors required for gastric cancer are poorly understood. Furthermore, it is not known at what stage in progression to gastric cancer that eradication of H. pylon would interrupt the carcinogenic process. Polyparasitism is also ubiquitous in developing populations where H. pylori is endemic. The investigators have developed a C57BL/6 mouse model of chronic H. pylori/felis gastritis that is characterized by the progressive development of gastric atrophy, intestinal metaplasia and invasive gastric cancer. The mechanism of lesion development appears to involve increased apoptosis, mucus neck proliferation, intestinal metaplasia leading to altered cellular differentiation and changes in mucin phenotype and progression of invasive cancer in submucosal vasculature. They have also investigated bacterial and environmental factors that influence disease pathogenesis by generating isogenic mutants lacking specific candidate virulence determinants and by maintaining Helicobacter infected animals on diets high in salt. They have recently shown that in mice coinfected with helicobacter and a helminth infection, H. polygyrus, the gastric cytokine Thl/Th2 profile switches and the gastric phenotype changes from a Thl to a Th2 type gastritis. They now propose to explore the effects of specific genetic alterations, environmental influences and coinfections on the mucosal response and progression of Helicobacter associated gastric lesions. Specifically, they will ask whether 1) progression of H. pylon gastritis can be interrupted at critical points in the disease by antimicrobials or therapeutic vaccination to prevent development of premalignant lesions and gastric adenocarcinoma in the gerbil and/or mouse model 2) Alternatively, do environmental factors such as dietary salt, accelerate or otherwise alter the carcinogenic process, and importantly does the strain of H. pylon (with and without specified pathogenic determinants) influence the outcome of gastric disease in the mouse and gerbil model 3) Does modulation of the Thl/Th2 axis of the immune system by various helminth infections influence the severity and progression of gastritis in rodent models. Overall, these rodent models of Helicobacter infection will be used to study the mechanism by which Helicobacter contributes to neoplasia, and the factors (host, bacteria, dietary or co-infections) which confer susceptibility and/or resistance to premalignant lesions and gastric cancer.